The invention relates to the novel use of PAF to increase yon Willebrand factor and/or Factor VIII in blood. One specific application is in the treatment of von Willebrand disease and of haemophilia A.
Haemophilia A is a sex linked bleeding disorder characterized by deficiency in factor VIII. Von Willebrand disease is a bleeding disorder characterized by deficiency in von Witlebrand factor (also referred to as vWf). While factor VIII is one of the essential proteins involved in the blood coagulation cascade, von Willebrand is a glycoprotein whose function in injury repair is limited to blood vessels. Von Willebrand factor causes platelet adhesion to the site of the. vascular injury.
The conventional treatments for both von Willebrand disease and haemophilia A have been the administration of von Willebrand factor and factor VIII respectively or the administration of DDAVP (1-deamino-8-D-arginine vasopressin), a synthetic vasopressin analogue or of AVP (arginine vasopressin) analogues or DDAVP analogues. The use of blood plasma containing factor VIII and/or von Willebrand factor has several disadvantages, one being the risk of acquiring infectious diseases such as hepatitis B, hepatitis C and HIV associated with the use of blood products and the fact that the concentration of factor VIII and von Willebrand factor in blood is very low.
The drawbacks associated with the use of blood products in the treatment of blood disorders led to the use of DDAVP. DDAVP has been found to increase the plasma concentration of yon Willebrand factor and factor VIII in patients with mild or moderate haemophilia A or von Willebrand disease and in normal individuals. In spite of the widespread use of DDAVP, its molecular mechanism of action has not been completely elucidated.
There are also a number of patents disclosing various agents for the treatment of haemophilia A and/or other bleeding disorders. By way of example, U.S. Pat. No. 5,171,844 issued on Dec. 15, 1992 discloses the use of derivatives and fragments of factor VIII for the treatment of haemophilia A. U.S. Pat. No. 5,091,363 issued on Feb. 25, 1991 discloses the use of a mixture comprising factor VIII, antithrombin III, phospholipid and calcium ions as well as factor IX for the treatment of haemophilia A. U.S. Pat. No. 5,180,583 issued on Jan. 19, 1993 discloses the use of a composition comprising factor VIIA for the treatment of von Willebrand disease while U.S. Pat. No. 4,501,731 issued on Feb. 26, 1985 discloses the use of factor X zymogen for the treatment of various bleeding disorders.